Posttranscriptional modifications in RNA serve numerous functions, including stabilization of tertiary structure, and enhancement of the fidelity of intermolecular interactions. The determination of new natural forms of modification in nucleic acids is an essential first step in understanding such structure-function relationships. Transfer and ribosomal RNA will be isolated and screened by combined liquid chromatography-mass spectrometry to determine the presence and structures of modified nucleosides. The structures of new nucleosides will be determined by mass spectrometry, NMR, and additional appropriate methods. In the case of tRNA emphasis will be placed on thermophilic archaebacteria, and the potential correlation of modifications with phylogenetic status and with structure stabilization at high temperature. Mass spectrometry with electrophoresis for sequence location of modified nucleosides in 16S ribosomal RNA. The structures of liposidomycins, nucleoside antibiotic inhibitors of bacterial cell wall biosynthesis, will be determined, primarily by tandem mass spectrometry.